Metagenomi Announces Preclinical Data for Lead Hemophilia A Program Demonstrating Durable Factor VIII (FVIII) Activity Levels through Twelve Months
03 Septiembre 2024 - 3:05PM
Metagenomi, Inc. (Nasdaq: MGX), a precision genetic medicines
company committed to developing curative therapeutics for patients
using its proprietary gene editing toolbox, today announced data
from an ongoing preclinical study designed to provide evidence
supporting the potential durability and safety of the company’s
hemophilia A gene editing investigational therapy, MGX-001.
“We are thrilled to achieve this preclinical milestone
supporting our recent decision to declare MGX-001 as our
development candidate for hemophilia A,” said Brian C. Thomas, PhD,
CEO and founder of Metagenomi. “We conducted this NHP study in
response to a competitive landscape where gene therapies have been
unable to achieve long term persistence of FVIII activity levels in
patients. Establishing proof-of-concept of site specific gene
integration and durable activity levels of FVIII in NHPs over
twelve months in hemophilia A represents an important validation of
our platform. Our goal for MGX-001 is to provide a one-time,
curative treatment for adults and children with hemophilia A.
Furthermore, we intend to leverage the MGX-001 editing platform to
pursue additional therapies for secreted protein disorders.”
The NHP study involved treating three NHPs with a single
intravenous dose of an adeno associated virus (AAV) containing a
FVIII donor template followed 35 days later by a single intravenous
dose of a lipid nanoparticle (LNP) containing a novel Metagenomi
nuclease and associated guide RNA targeting the first intron of the
albumin gene. Each animal received only a single dose of
dexamethasone prior to the AAV and LNP doses. The NHPs were then
followed for safety and donor FVIII activity. The NHPs also
underwent liver biopsy on Day 7 to evaluate editing and integration
efficiency. The study remains ongoing.
All NHPs demonstrated durable FVIII activity levels over the
twelve-month period. At the twelve-month time point two of the NHPs
had FVIII activity levels within normal/near normal range (82% and
41%) while the third NHP had FVIII activity level in the mild
hemophilia range (9%). Comparisons of mean values from the three to
six month time points to the nine to twelve month time points were
highly consistent, demonstrating no significant decline in
donor-derived FVIII activity levels. Liver biopsy data demonstrated
gene integration in the forward orientation at a frequency of 0.7%
to 2.9%; these values positively correlated with FVIII activity
levels. Treatment was generally well tolerated with findings
limited to moderate transient elevation of liver transaminases
following AAV and LNP administration. There were no notable
findings in total bilirubin or albumin levels or adverse clinical
observations.
This early NHP study was conducted without the benefit of
several subsequent optimizations of the therapeutic candidate
designed to enhance safety and efficacy in the clinic. For the
development candidate MGX-001, the company selected a bioengineered
FVIII construct designed to improve FVIII activity levels,
optimized the ratio of different LNP components and timing between
AAV and LNP administration, and enhanced aspects of the
manufacturing processes.
“The treatment of hemophilia, which has undergone many
transformative changes over the past 60 years, is poised for yet
another disruptive change: the use of genome editing, with site
specific integration of FVIII, to produce functional cures in
patients with hemophilia A. I am encouraged by the preclinical
progress in the genome editing space to potentially provide a new
path to a one-time, curative treatment option for both adults and
children in hemophilia A in the future,” said Dr. Glenn Pierce,
member of the Metagenomi Scientific Advisory Board.
The company will host a conference call at 8:30am ET, on
Wednesday, September 4, 2024. The registration link to the webcast
can be found at https://ir.metagenomi.co/.
About Hemophilia A
Hemophilia A is the most common X-linked inherited bleeding
disorder, caused by a large variety of mutations in the FVIII gene
leading to a loss of functional FVIII protein. Intracranial
bleeding is of greatest concern as this can lead to major morbidity
and mortality. Bleeding into joints leads to cumulative joint
damage and is a major cause of morbidity. Diagnosis typically
occurs in infancy due to exaggerated bleeding in response to minor
injury or routine medical procedures. Prevalence is estimated to be
up to 26,500 patients in the US and more than 500,000 patients
globally according to the World Federation of Hemophilia (WFH),
with the vast majority of patients being male.
About Metagenomi
Metagenomi is a precision genetic medicines company committed to
developing curative therapeutics for patients using its
proprietary, comprehensive metagenomics-derived toolbox. Metagenomi
is harnessing the power of metagenomics, the study of genetic
material recovered from the natural environment, to unlock four
billion years of microbial evolution to discover and develop a
suite of novel editing tools capable of correcting any type of
genetic mutation found anywhere in the genome. Its comprehensive
genome editing toolbox includes programmable nucleases, base
editors, and RNA and DNA-mediated integration systems (including
prime editing systems and clustered regularly interspaced short
palindromic repeat associated transposases). Metagenomi believes
its diverse and modular toolbox positions the company to access the
entire genome and select the optimal tool to unlock the full
potential of genome editing for patients. For more information,
please visit https://metagenomi.co.
Cautionary Note Regarding
Forward‐Looking
Statements
This press release contains “forward-looking statements” within
the meaning of Section 27A of the Securities Act of 1933 and
Section 21E of the Securities Exchange Act of 1934, each as
amended. Such statements, which are often indicated by terms such
as “anticipate,” “believe,” “could,” “estimate,” “expect,”
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“potential,” “predict,” “project,” “should,” “will,” “would”
and similar expressions, include, but are not limited to, any
statements relating to our growth strategy and product development
programs, including the timing of and our ability to conduct
IND-enabling studies, make regulatory filings such as INDs,
statements concerning the potential of therapies and product
candidates, including our development candidate, MGX-001,
statements concerning the timing of data presentations and
publications, and any other statements that are not historical
facts. Forward looking statements are based on management’s current
expectations and are subject to risks and uncertainties that could
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to differ materially from those currently anticipated include:
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Investor Contact:Simon Harnest - CIO, SVP
Investor Relationssimon@metagenomi.co
Media Contact:Ashlye Hodge - Communications
Managerashlye@metagenomi.co
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